rs2282537

Positions:

• chr11-120317262-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014352.4(POU2F3):​c.1169G>A​(p.Arg390Lys) variant causes a missense change. The variant allele was found at a frequency of 0.142 in 1,613,774 control chromosomes in the GnomAD database, including 17,547 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.11 (1189 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16358 hom.)
• Consequence: POU2F3 NM_014352.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.16

Genes affected

POU2F3 (HGNC:19864): (POU class 2 homeobox 3) This gene encodes a member of the POU domain family of transcription factors. POU domain transcription factors bind to a specific octamer DNA motif and regulate cell type-specific differentiation pathways. The encoded protein is primarily expressed in the epidermis, and plays a critical role in keratinocyte proliferation and differentiation. The encoded protein is also a candidate tumor suppressor protein, and aberrant promoter methylation of this gene may play a role in cervical cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

POU2F3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014118254).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU2F3	NM_014352.4	c.1169G>A	p.Arg390Lys	missense_variant	12/13	ENST00000543440.7	NP_055167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU2F3	ENST00000543440.7	c.1169G>A	p.Arg390Lys	missense_variant	12/13	1	NM_014352.4	ENSP00000441687.2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17163 AN: 152008 Hom.: 1189 Cov.: 32

Gnomad AFR AF: 0.0503

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0870

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.0962

GnomAD3 exomes AF: 0.139 AC: 34966 AN: 251472 Hom.: 2821 AF XY: 0.145 AC XY: 19721 AN XY: 135908

Gnomad AFR exome AF: 0.0483

Gnomad AMR exome AF: 0.0842

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.144

Gnomad SAS exome AF: 0.233

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.145 AC: 212172 AN: 1461648 Hom.: 16358 Cov.: 32 AF XY: 0.148 AC XY: 107494 AN XY: 727144

Gnomad4 AFR exome AF: 0.0489

Gnomad4 AMR exome AF: 0.0864

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.113 AC: 17158 AN: 152126 Hom.: 1189 Cov.: 32 AF XY: 0.115 AC XY: 8536 AN XY: 74364

Gnomad4 AFR AF: 0.0502

Gnomad4 AMR AF: 0.0868

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.134 Hom.: 1900

Bravo AF: 0.102

TwinsUK AF: 0.139 AC: 514

ALSPAC AF: 0.135 AC: 519

ESP6500AA AF: 0.0558 AC: 246

ESP6500EA AF: 0.143 AC: 1226

ExAC AF: 0.141 AC: 17115

Asia WGS AF: 0.178 AC: 619 AN: 3478

EpiCase AF: 0.133

EpiControl AF: 0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.14	.;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	0.016
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.86	D;D;D
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	.;L;.
PrimateAI	Uncertain	0.50	T
REVEL	Benign	0.15
Sift4G	Benign	0.87	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.068
MPC		0.30
ClinPred		0.011	T
GERP RS		4.5
Varity_R		0.27
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2282537; hg19: chr11-120187971; COSMIC: COSV52792269;